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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04457336




Registration number
NCT04457336
Ethics application status
Date submitted
25/06/2020
Date registered
7/07/2020
Date last updated
8/07/2025

Titles & IDs
Public title
A Ph2b to Evaluate Clinical Efficacy and Safety of Tildacerfont in Adult CAH
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) in Adult Subjects With Classic Congenital Adrenal Hyperplasia
Secondary ID [1] 0 0
CAHmelia 203
Secondary ID [2] 0 0
SPR001-203
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Congenital Adrenal Hyperplasia 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tildacerfont/Placebo

Experimental: Tildacerfont Group 1 - Tildacerfont administered daily via oral tablet for 12 weeks at dose level 1

Experimental: Tildacerfont Group 2 - Tildacerfont administered daily via oral tablet for 12 weeks at dose level 2

Experimental: Tildacerfont Group 3 - Tildacerfont administered daily via oral tablet for 70 weeks at dose level 3

Placebo comparator: Placebo - Placebo administered daily via oral tablet for 12 weeks.


Treatment: Drugs: Tildacerfont/Placebo
Tablet, administered daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic Congenital Adrenal Hyperplasia (CAH) Over 12 Weeks
Timepoint [1] 0 0
Baseline and 12 weeks of treatment (Week 18)
Secondary outcome [1] 0 0
To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic CAH Over 12 Weeks
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic CAH Over 12 Weeks
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
To Evaluate the Effect of Tildacerfont in Reducing 17-OHP in Participants With Classic CAH Over 12 Weeks
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
To Evaluate the Effect of Tildacerfont in Reducing 17-OHP in Participants With Classic CAH Over 12 Weeks
Timepoint [4] 0 0
12 weeks

Eligibility
Key inclusion criteria
1. Male and female subjects =18 years old at screening
2. Has a known childhood diagnosis of classic CAH due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or documented (at any time) elevated 17-OHP and currently treated with HC, HC acetate, prednisone, prednisolone, methylprednisolone (or a combination of the aforementioned GCs)
3. Has been on a stable, supraphysiologic dose of GC replacement (defined as =15 mg/day and =60 mg/day in HCe) for =1 month before screening
4. Has A4 >ULN at both screening and Week 4 (measured before any AM GC dose) if daily GC dose <30 mg OR has A4 >2.5x ULN at both screening and Week 4 (measured before any AM GC dose)
5. For subjects with the salt-wasting form of CAH, subject has been on a stable dose of mineralocorticoid replacement for =1 month before screening
6. Agrees to follow contraception guidelines. Male subjects must also agree to refrain from donating sperm throughout the treatment period and for 90 days after the last dose of study drug.
7. Is able to understand all study procedures and risks involved and provides written informed consent indicating willingness to comply with all aspects of the protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Has a known or suspected diagnosis of any other known form of classic CAH (not due to 21 hydroxylase deficiency)
2. Has a history that includes bilateral adrenalectomy or hypopituitarism
3. Has a history of allergy or hypersensitivity to tildacerfont, any of its excipients, or any other CRF1 receptor antagonist
4. Current treatment with dexamethasone as GC therapy for CAH

a. Prior treatment with dexamethasone is allowed as long as the transition to an alternative GC regimen (eg, HC, prednisone, or prednisolone) has resulted in a stable dose of GC replacement for =1 month before screening.
5. Is not adherent to GC or study drug dosing regimen during the Run-in Period (defined as taking <80% of expected doses based on drug accountability)
6. Shows clinical signs or symptoms of adrenal insufficiency
7. Has had a clinically significant unstable medical condition, medically significant illness, or chronic disease occurring within 30 days of screening, including but not limited to:

1. An ongoing malignancy or <3 years of remission history from any malignancy, other than successfully treated localized skin cancer
2. eGFR of <45 mL/min/1.73 m2
3. Current or history of liver disease (with the exception of Gilbert's syndrome).
4. History of alcohol or substance abuse within the last year, or any significant history of alcohol or substance abuse that would likely prevent the subject from reliably participating in the study, based on the opinion of the Investigator
5. Active hepatitis B, hepatitis C, or HIV at screening
6. Subjects who plan to undergo bariatric surgery during the study are excluded.
7. Any other condition that would impact subject safety or confound interpretation of study results
8. Psychiatric conditions, including but not limited to bipolar disorder, schizophrenia, or schizoaffective disorders that are not effectively controlled on medication and may have an adverse impact on study compliance. Symptoms including hallucinations, delusions, and psychosis are exclusionary. Additionally:

1. Increased risk of suicide based on the Investigator's judgment or the results of the C-SSRS conducted at screening and Week 6 (eg, C-SSRS Type 3, 4, or 5 ideation within the past 6 months or any suicidal behavior within the past 12 months)
2. HADS score >12 for either depression or anxiety at screening or Week 6
9. Has clinically significant abnormal ECG or clinical laboratory results. Abnormal results that must be reviewed and discussed with the Medical Monitor to determine eligibility for this study include but are not limited to:

1. Any clinically meaningful abnormal ECG results, including QTcF >450 ms for male participants or >470 ms for female participants
2. ALT >2x ULN
3. Total bilirubin >1.5x ULN
4. Total bile acids >5x ULN
10. Routinely works overnight shifts
11. Subjects with travel plans/work schedules that result in significant and frequent changes in time zones (>2 hours) will require Medical Monitor approval for enrollment.
12. Females who are pregnant or nursing
13. Use of any other investigational drug from 30 days or 5 half-lives (whichever is longer) before screening to the end of the study
14. Use of the following drugs from 30 days or 5 half-lives (whichever is longer) before Day 1 to the end of the study:

1. Rosiglitazone, aromatase inhibitors, testosterone, growth hormones, or any other medication or supplement that could impact subject safety or confound interpretation of study results
2. The following drugs:

i. Moderate to strong inhibitors and/or inducers of CYP3A4 ii. Sensitive substrates or narrow-therapeutic-range substrates of CYP3A4 (except hormonal contraception containing =35 µg ethinyl estradiol) iii. Sensitive substrates or narrow-therapeutic-range substrates of BCRP (except those that can be administered QD in the morning, separated by approximately 10 hours from evening administration of study drug)
15. Donation or receipt of blood from 90 days before Screening to the end of the study; donation or receipt of platelets, white blood cells, or plasma from 30 days before Screening to the end of the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/05/2024
Sample size
Target
Accrual to date
Final
96
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Spruce Study Site - Nedlands
Recruitment hospital [2] 0 0
Spruce study site - Brisbane
Recruitment hospital [3] 0 0
Spruce Study Site - Elizabeth Vale
Recruitment hospital [4] 0 0
Spruce Study Site - Melbourne
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Elizabeth Vale
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Nevada
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Rhode Island
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
Brazil
State/province [18] 0 0
Brasília
Country [19] 0 0
Brazil
State/province [19] 0 0
São Paulo
Country [20] 0 0
Canada
State/province [20] 0 0
Newfoundland and Labrador
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Ottawa
Country [23] 0 0
Canada
State/province [23] 0 0
Sherbrooke
Country [24] 0 0
Denmark
State/province [24] 0 0
Aarhus
Country [25] 0 0
Denmark
State/province [25] 0 0
Copenhagen
Country [26] 0 0
Estonia
State/province [26] 0 0
Tallinn
Country [27] 0 0
Estonia
State/province [27] 0 0
Tartu
Country [28] 0 0
Germany
State/province [28] 0 0
Munich
Country [29] 0 0
Ireland
State/province [29] 0 0
Dublin
Country [30] 0 0
Italy
State/province [30] 0 0
Milan
Country [31] 0 0
Italy
State/province [31] 0 0
Napoli
Country [32] 0 0
Italy
State/province [32] 0 0
Rome
Country [33] 0 0
Italy
State/province [33] 0 0
Torino
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seoul
Country [35] 0 0
Latvia
State/province [35] 0 0
Riga
Country [36] 0 0
Lithuania
State/province [36] 0 0
Kaunas
Country [37] 0 0
Netherlands
State/province [37] 0 0
Nijmegen
Country [38] 0 0
Poland
State/province [38] 0 0
Kraków
Country [39] 0 0
Poland
State/province [39] 0 0
Warsaw
Country [40] 0 0
Romania
State/province [40] 0 0
Bucharest
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Madrid
Country [43] 0 0
Spain
State/province [43] 0 0
Sevilla
Country [44] 0 0
Spain
State/province [44] 0 0
Tarragona
Country [45] 0 0
Sweden
State/province [45] 0 0
Falun
Country [46] 0 0
Sweden
State/province [46] 0 0
Stockholm
Country [47] 0 0
Switzerland
State/province [47] 0 0
Saint Gallen
Country [48] 0 0
Switzerland
State/province [48] 0 0
Zürich
Country [49] 0 0
Turkey
State/province [49] 0 0
Istanbul
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Birmingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Spruce Biosciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kyriakie Sarafoglou, M.D
Address 0 0
Dept. of Pediatrics, Divisions of Endocrinology and Genetics & Metabolism, Univ. of Minnesota
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04457336